(1) Field of the Invention
This invention relates to a process for the preparation of aspartylphenylalanine alkyl esters. More particularly, it relates to a process for preparing an .alpha.-L-aspartyl-L-phenylalanine lower alkyl ester from fumaric acid, ammonia and an L-phenylalanine lower alkyl ester by utilizing a microorganism.
(2) Description of the Prior Art
An .alpha.-L-aspartyl-L-phenylalanine lower alkyl ester (hereinafter referred to as ".alpha.-APE" for brevity), especially an .alpha.-L-aspartyl-L-phenylalanine methyl ester, is a valuable substance as a novel sweetening agent.
Several processes for the preparation of the .alpha.-APE are known. In one process, an N-protected-L-aspartic anhydride is reacted with a lower alkyl ester of L-phenylalanine to form an N-protected-.alpha.-APE and then the protecting group is removed to form an .alpha.-APE. In another process, an N-protected-L-aspartic acid is reacted with a lower alkyl ester of phenylalanine in the presence of a protease to form an N-protected-.alpha.-APE or an adduct of N-protected-.alpha.-APE with the lower alkyl ester of phenylalanine, and then, the protecting group is removed to form an .alpha.-APE.
The former process has a problem in that an N-protected-.beta.-APE is formed as a by-product together with the N-protected-.alpha.-APE. The latter process is advantageous in that the above problem does not rise and a racemic mixture can be used as the starting compound. In each process, however, the starting aspartic acid or its anhydride be used after the amino group has been protected with a protecting group such as a benzyloxycarbonyl group.
If the steps of introducing and removing an amino group-protecting group, which are indispensable in the conventional processes, can be omitted, this will be very advantageous from the industrial viewpoint because the steps of the process are simplified and the loss of the starting and intended compounds is minimized.